MUM-1 and bcl-2 Positive Primary Diffuse Large B Cell Non-Hodgkin's Lymphoma of the Colon.

Primary diffuse large B cell lymphoma (DLBCL) presents as a nodal and extranodal disease. The most common extranodal site is the gastrointestinal tract (GI), with the stomach most frequently involved, followed by the small bowel. Primary DLBCL of the large bowel accounts for 0.2%-1.2% of all colonic tumors. We present two patients who underwent radical resections of right colonic tumors. They were diagnosed with primary colonic DLBCL following histological and immunohistochemical testing of the excised tissues, and were determined as being in stage IIE of the disease. The tumors expressed CD20 markers. Both received multi-agent chemotherapy with combined immunotherapy and remain in complete remission at 4 and 5 years.

Decreased CD161 activating and increased CD158a inhibitory receptor expression on NK cells underlies impaired NK cell cytotoxicity in patients with multiple myeloma.

AIM: As innate immune cells natural killer (NK), NK-like T and CTLγδ are important in antitumour response in multiple myeloma (MM), the aim of this study was to investigate some functional and phenotypical characteristics of these cells in MM. METHODS: 29 patients with MM prior to therapy, in clinical stage I-III and 15 healthy controls (HCs) were investigated. Percent of immune cells in peripheral blood, NK cell activity, expression of activating (CD161) and inhibitory (CD158a, CD158b) NK cell receptors on CD3-CD16+ NK cells were evaluated using 51-chromium-release assay and by flow cytometry. Production of interleukin (IL) 2 and tumour necrosis factor (TNF)α was analysed in supernatants from in vitro activated peripheral blood mononuclear cells. RESULTS: In patients with MM the percent of NK cells and their two subsets did not differ from controls, while NK-like T and CTLγδ cells were significantly decreased. Significant impairment of NK cell cytotoxicity, CD107a expression and interferon γ intracellular level was also shown. There was a significant decrease in CD161 and an increase in CD158a receptor expression on NK cells in these patients. Also IL-2 production was lowest in clinical stage III. However, TNF-α production did not differ between patients and HCs. CONCLUSIONS: Altered expression of CD161 activating and CD158a KIR inhibitory receptor is responsible for impaired antitumour activity of NK cells in MM patients. These new biomarkers may be helpful for patient selection for immunotherapy with cytokines, and novel KIR blocking monoclonal antibodies that enhance NK cell antimyeloma activity and provide clinical benefit.

Association of Bax Expression and Bcl2/Bax Ratio with Clinical and Molecular Prognostic Markers in Chronic Lymphocytic Leukemia.

BACKGROUND: In chronic lymphocytic leukemia (CLL), in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role. AIM: The aim of this study was to investigate the association of pro-apoptotic Bax gene expression and Bcl2/Bax ratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase (LPL) gene expression. METHODS: We analyzed the expression of Bax mRNA and Bcl2/Bax mRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction. RESULTS: We detected significant Bax gene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevated Bcl2/Bax ratio (p=<0.001). Regarding the association with prognostic markers, the Bcl2/Bax ratio showed a negative correlation to lymphocyte doubling time (r=-0.307; p=0.0451), while high-level Bax expression was associated with LPL-positive status (p=0.035). Both the expression of Bax and Bcl2/Bax ratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance. CONCLUSIONS: Our results suggest that dysregulated expression of Bcl2 and Bax, which leads to a high Bcl2/Bax ratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL.

Appearance of estrogen positive bilateral breast carcinoma with HER2 gene amplification in a patient with aplastic anemia.

Immunosuppressive therapy is one of the standard therapy protocols for aplastic anemia (AA). However, immunosuppressive therapy and androgenic steroids can promote development of solid tumors such as squamous carcinoma, head and neck tumors, adenocarcinoma of the stomach, hepatocarcinoma and breast carcinoma in long surviving patients with aplastic anemia. We present here a rare case of a 56-year-old woman in whom bilateral adenocarcinoma of the breast developed 11 years after the start of immunosuppressive and androgenic steroid therapy for aplastic anemia. Histological examination showed invasive ductal carcinoma with intense nuclear staining for estrogen receptors. Her2 immunohistochemistry was positive for 80% of stained cells, and chromogenic in situ hybridization showed a high level of HER2 gene amplification. This case indicated that a new therapy option is needed for estimation and evaluation to avoid the consequence of cancer occurrence.

Expression of Bcl2L12 in chronic lymphocytic leukemia patients: association with clinical and molecular prognostic markers.

Dysregulation of apoptosis is a distinctive feature of chronic lymphocytic leukemia (CLL), although a unique mechanism underlying apoptosis resistance of CLL B lymphocytes has not been identified yet. Aberrant expression as well as genetic and epigenetic alterations of numerous genes involved in different pathways of apoptosis regulation has been described in CLL. Here, we report the expression analysis of Bcl2L12 (Bcl2-like 12), a novel apoptotic gene belonging to Bcl2 family, in 58 Serbian CLL patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed a significant overexpression of Bcl2L12 mRNA in CLL samples compared to non-leukemic samples, implying its role in the pathogenesis of the disease. Receiver operating characteristic (ROC) analysis showed that Bcl2L12 expression efficiently discriminates CLL cases from healthy controls. However, relatively homogenous Bcl2L12 mRNA expression among patients did not reflect their clinical characteristics (with the exception of lactate dehydrogenase status and time from diagnosis to treatment) and failed to show association with the most informative prognostic markers, namely the mutational status of rearranged immunoglobulin heavy chain variable region genes, CD38 and lipoprotein lipase gene (LPL) expression.

The influence of novel transcriptional regulatory element in intron 14 on the expression of Janus kinase 2 gene in myeloproliferative neoplasms.

The expression of Janus kinase 2 (JAK2) gene is altered in myeloproliferative neoplasms (MPN) and the regulation of transcription could be a mechanism that modulates JAK2 gene expression. We analyzed the transcriptional potential of single-nucleotide polymorphism (SNP) rs12343867 T > C in JAK2 intron 14, tagging 46/1 haplotype, and its influence on JAK2 gene expression. Functional analysis of JAK2 intron 14 was performed using the pBLCAT5 reporter system in K562 cells. Identification of the proteins binding to the intron 14 regulatory element was accomplished by electrophoretic mobility shift assay (EMSA) and supershift assays. Quantification of the expression of JAK2 gene in a cohort of 51 MPN patients and 12 healthy controls was performed by real-time quantitative polymerase chain reaction (RQ-PCR). Functional analysis revealed that the intronic DNA element harboring SNP rs12343867 T > C acts as a transcriptional repressor in vitro. The repressor activity was significantly attenuated by the presence of nucleotide C. Supershift analysis showed the enrolment of transcriptional factor Meis1 in this process. RQ-PCR experiments showed increased JAK2 expression in patients with the JAK2V617F mutation, with a significant difference between essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) patients. SNP rs12343867 showed no statistically significant influence on the expression of JAK2 gene in MNP patients.

Prognostic impact of NPM1 mutations in Serbian adult patients with acute myeloid leukemia.

Based on current findings, the presence of NPM1 mutations in acute myeloid leukemia (AML) patients is associated with an increased probability of complete remission (CR) and better overall survival (OS). We determined the incidence and prognostic relevance of NPM1 mutations, their association with FLT3 and IDH mutations, and other clinical characteristics in Serbian adult AML patients. Samples from 111 adult de novo AML patients, including 73 AML cases with a normal karyotype (NK-AML), were studied. NPM1, FLT3, and IDH mutations were detected by PCR and direct sequencing. NPM1 mutations were detected in 22.5% of patients. The presence of NPM1 mutations predicted a low CR rate and shorter OS. NPM1 mutations showed an association with both FLT3 and IDH mutations. Survival analysis based on NPM1/FLT3 mutational status revealed a lower OS for NPM1(+)/FLT3(-) compared to the NPM1(-)/FLT3(-) group in NK-AML patients. The lack of impact or unfavorable prognostic effect of NPM1 mutations found in this study can be assigned to a small cohort of analyzed AML patients, as can the presence of FLT3 and IDH mutations or other genetic lesions that cooperate with NPM1 mutations influencing prognosis.

Concomitant aberrant methylation of p15 and MGMT genes in acute myeloid leukemia: association with a particular immunophenotype of blast cells.

In this study, methylation-specific polymerase chain reaction (MS-PCR) was used to define the methylation status of the target promoter sequences of p15 and MGMT genes in the group of 21 adult patients with acute myeloid leukemia (AML). The incidence of aberrant hypermethylation of p15 gene (71 %) was higher comparing to MGMT gene (33 %), whereas concomitant methylation of both genes had 24 % of the patients. Although the incidence of cytogenetic abnormalities between the groups with a different methylation status of p15 and/or MGMT genes was not significantly different, we observed general trend of clustering of abnormalities with adverse prognosis into groups with concomitant hypermethylation of both genes and only p15 gene. Also, we showed that AML patients with concomitant methylation of p15/MGMT genes had a higher proportion of leukemic blast cells characterized with specific expression of individual leukocyte surface antigens (CD117(+)/CD7(+)/CD34(+)/CD15(-)), indicating leukemic cells as early myeloid progenitors. Although we could not prove that hypermethylation of p15 and/or MGMT genes is predictive parameter for response to therapy and overall survival, we noticed that AML patients with comethylated p15/MGMT genes or methylated p15 gene exhibited a higher frequency of early death, lower frequency of complete remissions as well as a trend for shorter overall survival. Assessing of the methylation status of p15 and MGMT genes may allow stratification of patients with AML into distinct groups with potentially different prognosis.

Overexpression of the novel member of the BCL2 gene family, BCL2L12, is associated with the disease outcome in patients with acute myeloid leukemia.

OBJECTIVES: BCL2L12 is a recently discovered and cloned gene from members of our research team. It is a novel member of the BCL2 gene family, members of which are implicated in different hematological malignancies. In the present study, we investigated and studied the expression profile of BCL2L12 in acute myeloid leukemia (AML). DESIGN AND METHODS: Total RNA was isolated from peripheral blood of 67 AML patients and healthy donors. The expression profile of BCL2L12 was studied using real-time PCR methodology (SYBR Green chemistry). We also evaluated the association of the BCL2L12 mRNA expression level with clinical and pathological disease parameters, as well with disease-free survival (DFS) and overall survival (OS), using the chi-square (χ(2)) test or the Fisher's exact test, where appropriate. RESULTS: Leukemia patients expressing high level of BCL2L12 were 3 times more likely to relapse (p=0.004) or die (p=0.007) than patients with low level of BCL2L12 expression. Additionally, statistically significant relationships were revealed between BCL2L12 expression level and CD117 expression, the presence of splenomegaly and chemotherapy response. CONCLUSIONS: Our results suggest that BCL2L12 can be considered as a new independent prognostic and chemotherapy response marker in AML.

Transformation of primary myelofibrosis with 20q- in Philadelphia-positive acute lymphoblastic leukemia: case report and review of literature.

A 56-year-old male with chronic idiopathic myelofibrosis and cytogenetic finding of 20q- after a period of 10 months developed acute Philadelphia-positive lymphoblastic leukemia. Immunophenotyping of peripheral blood by flow cytometry showed HLA-DR, CD34, CD19, CD22, CD10, CD33, and CD11b positivity. Cytogenetic analysis revealed the presence of 20q- and Philadelphia chromosome t(9;22)(q34:q11) at the time of disease transformation to ALL. The JAK2V617F mutation was not found. This is a very rare case of simultaneous presence of two cytogenetics abnormalities and evolution of primary idiopathic myelofibrosis to Philadelphia-positive acute lymphoblastic leukemia.

Induction chemotherapy versus palliative treatment for acute myeloid leukemia in a consecutive cohort of elderly patients.

A retrospective survey of 210 consecutive patients aged ≥ 65 years (median age 69 years, range 65-88 years) with acute myeloid leukemia (AML) diagnosed at a single center over a 6-year period (January 2001 to December 2006) is presented. De novo AML was diagnosed in 179 (85.2 %) patients and 31 (14.7 %) patients had a secondary AML. Twenty-three patients had M0 (11 %), 36 M1 (17.15 %), 57 M2 (27.1 %), eight M3 (3.8 %), 45 M4 (21.4 %), 31 M5 (14.8 %), one M6 (0.5 %), one M7 (0.5 %), and eight patients had unclassified myeloid leukemia (3.8 %) according to French-American-British (FAB) Study Group Classification. Eight patients with M3 (acute promyelocytic leukemia) were excluded from the study. Cytogenetic analysis was performed in 172/202 (85 %) patients. The normal karyotype was found in 81/172 (47 %), high risk aberrations in 32/172 (18.6 %), and favorable karyotype in 13/172 (7.5 %) patients. Supportive and palliative therapies were applied in 115 (56.9 %) patients, a no induction chemotherapy (NIC) group, and 87 (43.1 %) patients received induction chemotherapy (IC group). Complete remission (CR) was achieved in 45/87 (51.7 %) in the IC group and in 5/115 (4.3 %) in the NIC group of patients. After a median follow up of 4 years, 194 (96 %) patients died. The variables significantly associated with a longer overall survival (OS) by univariate analysis were an age of <75 years, a better ECOG performance status (PS) (p = 0.000, CI 95.0 %, 1.358-2.049), a serum LDH activity <600 U/l (p = 0.000, CI 95.0 %, 1.465-2.946), lower white blood cell (WBC) count at diagnosis (p = 0.011, CI 95.0 %, 1.102-2.100), lower comorbidity HCT-CI index (p = 0.000, CI 95 % 2.209-3.458), absence of splenomegaly (p = 0.015, CI 95.0 %, 1.082-2.102) and hepatomegaly (p = 0.008, CI 95.0 %, 1.125-2.171), and no preceding nonhematological malignancy. Multivariate analysis showed that significant factors affecting OS in the IC group were achievement of CR (p = 0.000), the ECOG PS (p = 0.045) and the ECOG PS (p = 0.000), and HCT-CI (p = 0.000) in the NIC group of elderly patients. The present study suggests that a subgroup of elderly patients with both ECOG PS and HCT-CI ≤ 2 at presentation may be eligible for intensive induction chemotherapy.

Reversal of FLT3 mutational status and sustained expression of NPM1 mutation in paired presentation, and relapse samples in a patient with acute myeloid leukemia.

We report a case of de novo acute myeloid leukemia (AML) with unstable FLT3 gene mutations and stable NPM1 mutation. FLT3/D835 and NPM1 (Type A) mutations were detected upon diagnosis. During the relapse, the FLT3/D835 mutation changed to an FLT3/ITD mutation while the NPM1 (Type A) mutation was retained. Cytogenetic analyses showed the normal karyotype at diagnosis and relapse. Our findings raise interesting questions about the significance of these mutations in the leukemogenic process, about their stability during the evolution of the disease, and regarding the selection of appropriate molecular markers for the monitoring of minimal residual disease.

Mutational status and gene repertoire of IGHV-IGHD-IGHJ rearrangements in Serbian patients with chronic lymphocytic leukemia.

UNLABELLED: The mutational status and configuration of immunoglobulin heavy variable (IGHV) gene rearrangements was analyzed in 85 Serbian patients with chronic lymphocytic leukemia (CLL). We found that 55.3% of cases belonged to mutated and 44.7% to unmutated CLL, progressive disease predominating in the unmutated subset. IGHV gene use resembled that obtained for Mediterranean countries, except for underrepresentation of the IGHV4 subgroup in our cohort. BACKGROUND: Chronic lymphocytic leukemia (CLL) results from the clonal expansion of mature B lymphocytes and is characterized by extreme clinical heterogeneity. One of the most reliable prognostic markers in chronic lymphocytic leukemia (CLL) is the mutational status of immunoglobulin heavy variable (IGHV) genes, which defines 2 subsets, mutated CLL (M-CLL) and unmutated CLL (U-CLL), with different clinical courses. Biased IGHV gene use between M-CLL and U-CLL clones, as well as population differences in the IGHV gene repertoire have been reported. PATIENTS AND METHODS: In this study, mutational status and configuration of IGHV-IGHD-IGHJ rearrangements in 85 Serbian patients were analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing methodology. RESULTS: We found that 55.3% of cases belonged to M-CLL and 44.7% belonged to U-CLL, with progressive disease predominating in the unmutated subset. Most frequently expressed was the IGHV3 subgroup (55.7%), followed by IGHV1 (27.3%), IGHV4 (12.5%), IGHV5 (2.3%), IGHV2 (1.1%), and IGHV6 (1.1%). The distribution of IGHD subgroups was as follows: IGHD3, 39.1%; IGHD2, 21.8%; IGHD6, 12.6%; IGHD1, 10.3%; IGHD4, 8%; IGHD5, 6.9%; and IGHD7, 1.1%. The most frequent IGHJ gene was IGHJ4 (48.9%), followed by IGHJ6 (28.4%), IGHJ3 (11.4%), and IGHJ5 (11.4%). In 15.3% of cases, heavy complementarity-determining region 3 (VH CDR3) amino acid sequences could be assigned to previously defined stereotyped clusters. CONCLUSIONS: Our study showed a strong correlation between IGHV gene mutational status and clinical course of CLL. IGHV gene use was comparable to that obtained for Mediterranean countries, with the exception of the IGHV4 subgroup, which was underrepresented in our cohort.

Central nervous system relapse in CD56+, FLT3/ITD+ promyelocytic leukemia.

Central nervous system (CNS) involvement in acute promyelocytic leukemia (APL) is rare and tends to be seen mostly following treatment with all-trans retinoic acid (ATRA), due to prolonged patient survival and poor penetration of the drug in the CNS. At least 10% of extramedullary relapses in APL involve the CNS, and associated factors include an increased age, the BCR isoform, the development of differentiation syndrome, a high white cell count at presentation and hemorrhage into the CNS during induction therapy. We present the case of a patient with high-risk APL, CD56+, CD2+ in whom a CNS relapse was diagnosed through the presence of a PML/RARα rearrangement on PCR of the cerebrospinal fluid (CSF).

[Primary Burkitt's lymphoma of the stomach].

INTRODUCTION: Burkitt's lymphoma belongs to the group of non-Hodgkin's lymphomas with B immunophenotypic features of lymphoma cells. It has tendency for extranodal localization primarily in the gastrointestinal tract and retroperitoneum. Primary Burkitt's lymphoma of the stomach is very rare. Stomach is most frequently involved secondarily, growing from intrabdominal tumorous mass into the stomach. CASE OUTLINE: The authors present a 30-year-old male in whom after 6 months duration of temporarily melaenas the diagnosis of Burkitt's lymphoma was established by endoscopic examination and biopsy of ulceroinfiltrative lesion on the antral part of the stomach. The patient was in clinical stage IIE. After one cycle of chemotherapy according to protocol R-HyperCVAD, a subtotal distal gastrectomy and additional three cycles of the same chemotherapeutic protocol a complete remission was achieved. CONCLUSION: Burkitt's lymphoma is a highly aggressive non-Hodgkin's lymphoma often present in extranodal sites. It should be treated with systemic intensive chemotherapy and surgical removal of tumorous mass when possible. Long-term survival using the combination therapy is possible to achieve in 40-80% of patients.

Favourable prognostic factors in therapy related acute myeloid leukaemia.

INTRODUCTION: Therapy related acute myeloid leukaemia (t-AML) is a distinct clinical entity recognized by the World Health Organization classification occurring after chemotherapy and/or radiation treatment administered for a previous disease. T-AML is characterised by pancytopenia, three-lineage myelodysplasia, high frequency of unfavourable cytogenetics and short survival. OBJECTIVE: The aim of this study was to analyse clinical, cytogenetic, and cytological characteristics of t-AML and their impact on survival. METHODS: Seventeen patients with t-AML (8 male and 9 female; median age 59 years) were identified among 730 consecutive patients with acute myeloid leukaemia. The degree of three-lineage dysplasia as well as haematological, cytological and cytogenetic analyses, were assessed by standard methods. RESULTS: The patients survived a median of 62.5 days with the 10% probability of survival during two years. Prognostically favourable factors were a higher percentage of dysplastic granulocytic cells, age less than 60 years, and presence of prognostically favourable karyotype inv(16), t(15;17), t(8;21). CONCLUSION: The stated prognostic factors that include age, cytogenetics findings and granulocytic dysplasia analysis could contribute to adequate risk stratification of t-AML, though fuller results would require additional analyses.

Response to cladribine in patient with systemic mastocytosis.

INTRODUCTION: Systemic mastocytosis is a heterogeneous group of hematological disorders characterized by accumulation of mast cells in different organs. CASE REPORT: A 41-year-old woman presented with a three-year history of fatigue, occasional diarrhea, mild fever, skin rash and splenomegaly. Laboratory results showed severe anemia and thrombocytopenia. Cytological and histological investigation of bone marrow showed a marked increase of mast cells infiltration with following immunophenotype: CD117+, CD68+, CD34-, MPO-, CD15-. She was treated with cladribine 0.15 mg/kg body weight from day 1 to day 5, a total of six cycles, and achieved a good partial response, transfusion independency and normalization of spleen size. Although the patient responded to the treatment, the relapse with splenomegaly and bicytopenia was observed after 10 months. CONCLUSION: Cladribine therapy was efficient in the patient' with systemic mastocytosis but the response was transient, so there is the need to search for new therapeutic options and more effective strategies in the treatment of patients with aggressive mast cell disorders.

[Diffuse large cell lymphoma and colon adenocarcinoma in patient with Waldenström's macroglobulinaemia].

INTRODUCTION: Waldenström's macroglobulinaemia is a rare B cell lymphoproliferative disorder characterized by lymphoplasmocyte bone marrow infiltration and monoclonal IgM gammopathy. In the majority of cases, Waldenström's macroglobulinaemia is a chronic disease with variable course. Therapy consists of alkylating agents, purine analogs and antiCD20 monoclonal antibody. In the literature, there have been descriptions of rare cases of progression of Waldenström's macroglobulinaemia to aggressive lymphoma, as well as secondary carcinoma in the patients after treatment of macroglobulinaemia. CASE OUTLINE: A 63-year-old patient was diagnosed with serum monoclonal IgM kappa gammopathy (Waldenström's macroglobulinaemia). Chemotherapy was applied and a good clinical and haematological response had been achieved. Ten years later, the patient was diagnosed with colon adenocarcinoma as a secondary malignancy, and operated on. Within one month, the patient rapidly developed a large neck tumour mass. Tumour biopsy revealed the diagnosis of diffuse large B-cell lymphoma with the expression of monoclonal lambda chain, which more likely pointed out to coexistence of two different B cell lymphoproliferative disorders, rather than the transformation of Waldenström's macroglobulinaemia to aggressive lymphoma. The patient was treated with chemotherapy following R-CHOP protocol, and clinical remission was achieved. Seven months later, despite the successful treatment of lymphoproliferative disorder, dissemination of adenocarcinoma led to the lethal outcome. CONCLUSION: The patient was diagnosed with a rare occurrence of three neoplastic diseases: Waldenstrom's macroglobulinaemia, colon adenocarcinoma and diffuse large B cell lymphoma. The possible mechanisms of the combined appearance of lymphoproliferative and other malignant diseases include the previous treatment with alkylating agents, genetic, immunomodulatory and environmental factors.

Alveolar granulocytic sarcoma of the mandible in a patient with HIV.

BACKGROUND: Granulocytic sarcoma (chloroma) occurs primarily in patients with acute myelogenous leukemia although it can also appear in connection with other myeloproliferative disorders. CASE REPORT: We present the case of a 52-year-old human immunodeficiency virus (HIV)-positive female patient with a CD4+ count of 321 cells/ml, who developed an alveolar granulocytic sarcoma of the mandible. Pathological analysis of the tumor mass showed an infiltrate of immature cells which were positive for CD13, CD33, CD15, CD11b, and CD64, and negative for CD34, CD117, and HLA-DR. The patient achieved complete remission following a 1-week course of chemotherapy, however, 7 months later she developed a second granulocytic sarcoma in the left soleus muscle. The absolute CD4+ count had now reduced to 3 cells/ml with an inversion in the Th/Ts index (0.01), and she died of gram-negative sepsis 1 month later. CONCLUSIONS: Granulocytic sarcoma is extremely rare in patients with HIV. The case is discussed with reference to the literature.